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Tuesday, June 10, 2014
Accelerated senescence of cord blood endothelial progenitor cells in premature neonates is driven by SIRT1 decreased expression.
Epidemiological and experimental studies indicate that early vascular dysfunction occurs in low-birth-weight subjects, especially preterm (PT) infants. We recently reported impaired angiogenic activity of endothelial colony-forming cells (ECFCs) in this condition. We hypothesized that ECFC dysfunction in PT might result from premature senescence and investigated the underlying mechanisms. Compared with ECFCs from term neonates (n = 18), ECFCs isolated from PT (n = 29) display an accelerated senescence sustained by growth arrest and increased senescence-associated β-galactosidase activity. Increased p16(INK4a) expression, in the absence of telomere shortening, indicates that premature PT-ECFC aging results from stress-induced senescence. SIRT1 level, a nicotinamide adenine dinucleotide-dependent deacetylase with anti-aging activities, is dramatically decreased in PT-ECFCs and correlated with gestational age. SIRT1 deficiency is subsequent to epigenetic silencing of its promoter. Transient SIRT1 overexpression or chemical induction by resveratrol treatment reverses senescence phenotype, and rescues in vitro PT-ECFC angiogenic defect in a SIRT1-dependent manner. SIRT1 overexpression also restores PT-ECFC capacity for neovessel formation in vivo. We thus demonstrate that decreased expression of SIRT1 drives accelerated senescence of PT-ECFCs, and acts as a critical determinant of the PT-ECFC angiogenic defect. These findings lay new grounds for understanding the increased cardiovascular risk in individuals born prematurely and open perspectives for therapeutic strategy.
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Proud to announce the release of the Encyclopedia of Biomedical Gerontology, edited by professor Suresh Rattan. #gerontology, #aginghttps://t.co/fLsaMqQJxW
Go Daphnia! Does genome size matter? this water flea has 8000 more genes than human http://bit.ly/hYpD2H #genome— Juliana A (@Symbiologica) February 4, 2011
In 1900 the average lifespan in the US was 47.— Quirky Facts (@QuirkFacts) February 22, 2015
Regardless whether you put #aging out of your mind or not you're going to continue to age until it becomes a problem. Instead of putting it out of your mind until the problem's at your doorstep why not try to reverse it? Indeed biogerontology & biomedical gerontology are on it.— Zena O'Brien #GeneralStrike (@ZenaMOBrien) January 10, 2019
pic.twitter.com/KHwpVKfIt9— Elsevier Major Reference Works (@ElsevierMRW) December 9, 2019
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